4.8 Article

Discovering dominant tumor immune archetypes in a pan-cancer census

Journal

CELL
Volume 185, Issue 1, Pages 184-+

Publisher

CELL PRESS
DOI: 10.1016/j.cell.2021.12.004

Keywords

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Funding

  1. AbbVie
  2. Amgen
  3. Bristol-Myers Squibb
  4. Pfizer
  5. NIH [R01CA197363, U01CA217864]
  6. NCI [R01 CA178015, CA222862, CA227807, CA239604, CA230263, U24 (CA210974), U54 (CA224081), P30 (P30CA082103)]

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This study identifies common patterns of the immune system in different types of cancer and proposes strategies to modulate tumor immunity for improved therapy. The findings provide new insights into cancer immunity and offer a rational approach to enhance treatment.
Cancers display significant heterogeneity with respect to tissue of origin, driver mutations, and other features of the surrounding tissue. It is likely that individual tumors engage common patterns of the immune system-here archetypes-creating prototypical non-destructive tumor immune microenvironments (TMEs) and modulating tumor-targeting. To discover the dominant immune system archetypes, the University of California, San Francisco (UCSF) Immunoprofiler Initiative (IPI) processed 364 individual tumors across 12 cancer types using standardized protocols. Computational clustering of flow cytometry and transcriptomic data obtained from cell sub-compartments uncovered dominant patterns of immune composition across cancers. These archetypes were profound insofar as they also differentiated tumors based upon unique immune and tumor gene expression patterns. They also partitioned well-established classifications of tumor biology. The IPI resource provides a template for understanding cancer immunity as a collection of dominant patterns of immune organization and provides a rational path forward to learn how to modulate these to improve therapy.

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